A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents

Abstract

A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis. A new scheme determining outliers by “leave-one-out” (LOO) cross-validation coefficient ( q 2 n - i ) was suggested and successfully used. In the established optimal equation (excluding two outliers), the steric parameter ( MR R) and the net charge ( Q FR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (lg P )2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds. The fitting correlation coefficient ( R 2) and the cross-validation coefficient (q2) values are 0.883 and 0.797, respectively. It indicates that this model has a significantly statistical quality and an excellent prediction ability. Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.